rTMS for Cognitive Impairment in Parkinson's Disease

(TMSCogReP Trial)

Recruiting at 1 trial location

Overseen By Elyse R Walsh, DPT

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: VA Office of Research and Development

Must not be taking: Tricyclics, Neuroleptics, others

Disqualifiers: Dementia, Severe depression, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 8 weeks

56 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to examine safety, feasibility, and the behavioral and brain effects of a non-invasive treatment, repetitive transcranial magnetic stimulation (rTMS), for Veterans with Parkinson's disease or atypical parkinsonism and mild impairments in their thinking. The hypothesis is that rTMS can improve thinking for people with Parkinson's disease or atypical parkinsonism who are experiencing mild problems with their thinking ability.

Will I have to stop taking my current medications?

You will need to stay on your current medications without any changes in type or dose during the trial.

What data supports the effectiveness of the treatment rTMS for cognitive impairment in Parkinson's Disease?

Research shows that repetitive transcranial magnetic stimulation (rTMS) can improve motor function in Parkinson's disease, but its effects on cognitive function are not significant. Some studies suggest that rTMS may help with daily activities and motor skills, but more research is needed to confirm its benefits for cognitive impairment. ^{1 2 3 4 5}

Is rTMS safe for humans?

Repetitive transcranial magnetic stimulation (rTMS) is generally considered safe for humans, with studies showing it can be safely administered to patients with Parkinson's disease and other conditions. However, there is a slight risk of seizures and other adverse events, so safety guidelines have been established to minimize these risks. ^{2 6 7 8 9}

How does the treatment rTMS differ from other treatments for cognitive impairment in Parkinson's disease?

Repetitive Transcranial Magnetic Stimulation (rTMS) is unique because it uses magnetic fields to stimulate specific areas of the brain, potentially improving motor and cognitive functions in Parkinson's disease. Unlike traditional medications, rTMS is non-invasive and can target deep brain structures, offering a novel approach to modulating brain activity and enhancing cortical plasticity. ^{1 3 4 10 11}

Research Team

Sandra L. Kletzel, PhD BA

Principal Investigator

Edward Hines Jr. VA Hospital, Hines, IL

Eligibility Criteria

This trial is for Veterans over 50 with Parkinson's disease who have mild cognitive impairment, can speak and read English, and are treated at Hines VA Hospital or Jesse Brown VA Medical Center. Participants must be on stable medication that won't change during the study. Those with severe depression, dementia, certain implants, history of seizures or metal in their body cannot join.

Inclusion Criteria

My current medication is stable and will not change during the trial.

I am 50 years old or older.

My medication and its dose have been stable and will remain so during the trial.

Exclusion Criteria

You have memory and thinking problems.

Your motor threshold cannot be measured accurately for determining the dosage of rTMS.

I am not taking medications known to increase the risk of seizures.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either active or sham rTMS treatment to assess cognitive outcomes and brain connectivity

8 weeks

Regular sessions for rTMS treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment, including a neurocognitive battery assessment

4 weeks

1 visit (in-person) for follow-up assessment

Treatment Details

Interventions

• rTMS

Trial Overview The trial tests if repetitive transcranial magnetic stimulation (rTMS) using a MagVenture MagProX100 stimulator can improve thinking abilities in those with Parkinson's experiencing mild cognitive issues. It assesses the safety and effects of rTMS on behavior and brain function.

Participant Groups

Group I: active rTMS Experimental Treatment 1 Intervention

For active rTMS, a butterfly coil and MagVenture MagProX100 stimulator (MagVenture, Falun, Denmark) will be used. One rTMS session will consist of 40 trains of 5sec each at 110% of resting motor threshold and 15Hz will be provided at the left DLPFC.

Group II: sham rTMS Placebo Group 1 Intervention

For sham rTMS, the procedure will be carried out at the left DLPFC but a sham coil will be used. The MagVenture coil has an active side and a placebo side allowing a double-blind study to be conducted. The sham system looks, sounds and feels like active rTMS.

rTMS is already approved in United States, European Union for the following indications:

Approved in United States as rTMS for:

• Obsessive-Compulsive Disorder (OCD)
• Major Depressive Disorder
• Migraines
• Smoking cessation

Approved in European Union as rTMS for:

• Obsessive-Compulsive Disorder (OCD)
• Major Depressive Disorder

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Findings from Research

Repetitive transcranial magnetic stimulation (rTMS) has shown a significant positive effect on global cognitive function in Parkinson's disease patients, particularly measured by the mini-mental state examination (MMSE) across 14 studies with 173 subjects.

High-frequency rTMS targeting the dorsolateral prefrontal cortex (DLPFC) specifically improved executive function, while other cognitive domains like memory, attention, and language did not show significant benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of rTMS on Parkinson's cognitive function: a systematic review and meta-analysis. Jiang, Y., Guo, Z., McClure, MA., et al.[2021]

In a study involving 26 patients with mild to moderate Parkinson's disease, 50-Hz repetitive transcranial magnetic stimulation (rTMS) was found to be safe, with no adverse effects or increased risk of cortical excitability.

However, the treatment did not lead to significant improvements in motor symptoms such as gait and bradykinesia, although there was a brief improvement in daily living activities, suggesting that longer or different rTMS protocols may be needed for better efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Controlled study of 50-Hz repetitive transcranial magnetic stimulation for the treatment of Parkinson disease. Benninger, DH., Iseki, K., Kranick, S., et al.[2021]

In a study involving 12 patients with idiopathic Parkinson's disease, 0.2 Hz repetitive transcranial magnetic stimulation (rTMS) to the frontal cortex significantly improved daily living activities and motor scores, while occipital rTMS showed no significant clinical effects.

The study suggests that rTMS may have indirect effects on subcortical structures that contribute to symptom improvement, despite reduced regional cerebral blood flow (rCBF) in the stimulated areas, indicating a complex mechanism of action that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of successive repetitive transcranial magnetic stimulation on motor performances and brain perfusion in idiopathic Parkinson's disease. Ikeguchi, M., Touge, T., Nishiyama, Y., et al.[2019]

In a study involving 6 patients with Parkinson's disease and 10 normal controls, repetitive transcranial magnetic stimulation (rTMS) significantly improved choice reaction time and movement time in patients without affecting their error rate, suggesting enhanced motor function.

The rTMS treatment also improved performance on a grooved peg-board test in Parkinson's patients, particularly when they were not on medication, indicating its potential as a therapeutic intervention for motor symptoms in Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Akinesia in Parkinson's disease. II. Effects of subthreshold repetitive transcranial motor cortex stimulation. Pascual-Leone, A., Valls-Solé, J., Brasil-Neto, JP., et al.[2019]

Repetitive transcranial magnetic stimulation (rTMS) and transcranial electrical stimulation (TES) both showed significant improvements in motor function for Parkinson's disease patients compared to sham stimulation, with rTMS having a moderate effect size (SMD = 0.394) and TES showing a larger effect (SMD = 0.611).

Neither rTMS nor TES were found to improve cognitive function in patients with Parkinson's disease, indicating that while these therapies can help with motor symptoms, they may not address cognitive deficits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using non-invasive transcranial stimulation to improve motor and cognitive function in Parkinson's disease: a systematic review and meta-analysis. Goodwill, AM., Lum, JAG., Hendy, AM., et al.[2022]

Deep repetitive transcranial magnetic stimulation (drTMS) is safe for patients with various Parkinson Syndromes and can effectively reduce their self-reported motor symptom severity and depression, based on a retrospective analysis of 21 patients.

The treatment showed more significant benefits in older patients with Parkinson's disease, although it did not demonstrate any improvement in cognitive performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Deep Repetitive Transcranial Magnetic Stimulation (drTMS) against Medical Refractory Symptoms in Parkinson Syndromes: First German Real-World Data with a Specific H5 Coil. Cont, C., Lehto, A., Stute, N., et al.[2022]

A review of 84 single pulse and paired-pulse TMS studies with 1091 Parkinson's disease patients, and 77 repetitive TMS studies with 1137 patients, found a very low risk of adverse events, with no seizures reported.

The overall risk of adverse events from rTMS was 0.040 per patient, with common side effects being mild and transient, such as headaches and scalp pain, indicating that TMS is generally safe for Parkinson's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcranial magnetic stimulation in Parkinson's disease: a review of the literature. Vonloh, M., Chen, R., Kluger, B.[2021]

Repetitive transcranial magnetic stimulation (rTMS) has gained popularity for its ability to modulate brain activity, but safety considerations are crucial, especially with the recent updates to safety guidelines published in 2021.

The guidelines emphasize the importance of screening for risks, monitoring for adverse events, and specific safety measures when using rTMS, particularly in patients with conditions like stroke and traumatic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. Kim, WS., Paik, NJ.[2023]

Repetitive transcranial magnetic stimulation (rTMS) is generally a well-tolerated treatment for depression, with mild side effects like headaches being the most common, while severe adverse effects are rare.

Special precautions are necessary for certain groups, such as adolescents, pregnant women, and individuals with metal implants, but with proper assessment and monitoring, rTMS can be safely administered to many patients with depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation (TMS) safety: a practical guide for psychiatrists. Taylor, R., Galvez, V., Loo, C.[2019]

Repetitive transcranial magnetic stimulation (rTMS) at different frequencies (1 Hz and 5 Hz) significantly improved motor function and daily living activities in patients with Parkinson's disease, as evidenced by clinical rating scores and motor dexterity assessments in a study involving 50 participants.

The study demonstrated that rTMS induced changes in brain activity, with increased blood oxygen level-dependent (BOLD) signals in motor areas, indicating that rTMS can promote cortical plasticity and potentially restore motor function in Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanisms of 1 Hz Inhibitory and 5 Hz Excitatory Repetitive Transcranial Magnetic Stimulations in Parkinson's Disease: A Functional Magnetic Resonance Imaging Study. Bhat, P., Goyal, V., Kumaran, SS., et al.[2023]

In a study involving 27 patients with Parkinson's disease, repetitive deep transcranial magnetic stimulation (rDTMS) using H-coils was found to be safe, with no adverse events reported during 12 treatment sessions.

Patients experienced a significant improvement in motor symptoms, with an average reduction of 10.8 points on the motor UPDRS scale after treatment, indicating the potential efficacy of rDTMS as an add-on therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Excitatory deep repetitive transcranial magnetic stimulation with H-coil as add-on treatment of motor symptoms in Parkinson's disease: an open label, pilot study. Spagnolo, F., Volonté, MA., Fichera, M., et al.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Effect of rTMS on Parkinson's cognitive function: a systematic review and meta-analysis. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Controlled study of 50-Hz repetitive transcranial magnetic stimulation for the treatment of Parkinson disease. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of successive repetitive transcranial magnetic stimulation on motor performances and brain perfusion in idiopathic Parkinson's disease. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Akinesia in Parkinson's disease. II. Effects of subthreshold repetitive transcranial motor cortex stimulation. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Using non-invasive transcranial stimulation to improve motor and cognitive function in Parkinson's disease: a systematic review and meta-analysis. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Safety of Deep Repetitive Transcranial Magnetic Stimulation (drTMS) against Medical Refractory Symptoms in Parkinson Syndromes: First German Real-World Data with a Specific H5 Coil. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Safety of transcranial magnetic stimulation in Parkinson's disease: a review of the literature. [2021]

8. Korea (South) pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation (TMS) safety: a practical guide for psychiatrists. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Mechanisms of 1 Hz Inhibitory and 5 Hz Excitatory Repetitive Transcranial Magnetic Stimulations in Parkinson's Disease: A Functional Magnetic Resonance Imaging Study. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Excitatory deep repetitive transcranial magnetic stimulation with H-coil as add-on treatment of motor symptoms in Parkinson's disease: an open label, pilot study. [2018]